Glaser G, Giloh H, Kasir J, Gross M, Mager J
Biochem J. 1980 Dec 15;192(3):793-800. doi: 10.1042/bj1920793.
Addition of glucose to Ehrlich-Landschütz ascites tumour cells preincubated for 30-60 min in phosphate-buffered Krebs-Ringer salt solution ("starved cells") resulted within 1-2 min in an approx. 90% decline of their ATP content and a massive accumulation of fructose 1,6-bisphosphate. These alterations, which took place under both aerobic and anaerobic conditions, were followed by a gradual spontaneous recovery with restoration of normal ATP and fructose 1,6-bisphosphate values. The transient derangement of the energy metabolism after glucose addition to starved ascites tumour cells by preventable by simultaneous addition of pyruvate or 2-oxobutyrate, or by preincubating the cells in the presence of glucose. The protective effect of pyruvate was duplicated by addition of phenazine methosulphate or NAD+ to the incubation medium. The data seem to warrant the conclusion that the glucose-induced ATP depletion is determined by a blockade of glycolysis at the stage of glyceraldehyde phosphate dehydrogenase caused by the failure of the cells to oxidize the NADH produced in the same reaction. The continued unrestrained action of 6-phosphofructokinase results in accumulation of fructose 1,6-bisphosphate, which constitutes a trap for the high-energy phosphate bonds of ATP. The primary metabolic disturbance appears to consist of a transient inhibition of pyruvate kinase with the resultant inability of the cells to maintain an unimpaired supply of pyruvate, as required for the lactate dehydrogenase-mediated oxidation of NADH. The regulatory mechanism underlying this phenomenon is discussed.
将葡萄糖添加到在磷酸盐缓冲的克雷布斯 - 林格盐溶液中预孵育30 - 60分钟的艾氏 - 兰施胡茨腹水肿瘤细胞（“饥饿细胞”）中，在1 - 2分钟内导致其ATP含量下降约90%，并大量积累1,6 - 二磷酸果糖。这些变化在有氧和无氧条件下均会发生，随后会逐渐自发恢复，ATP和1,6 - 二磷酸果糖的值恢复正常。通过同时添加丙酮酸或2 - 氧代丁酸，或在葡萄糖存在下预孵育细胞，可以防止向饥饿腹水肿瘤细胞添加葡萄糖后能量代谢的短暂紊乱。向孵育培养基中添加吩嗪硫酸甲酯或NAD⁺可复制丙酮酸的保护作用。数据似乎足以得出结论，葡萄糖诱导的ATP消耗是由细胞无法氧化同一反应中产生的NADH导致磷酸甘油醛脱氢酶阶段糖酵解受阻所决定的。6 - 磷酸果糖激酶不受抑制的持续作用导致1,6 - 二磷酸果糖积累，这构成了ATP高能磷酸键的陷阱。主要的代谢紊乱似乎包括丙酮酸激酶的短暂抑制，导致细胞无法维持乳酸脱氢酶介导的NADH氧化所需的丙酮酸的正常供应。讨论了这一现象背后的调节机制。
